H E A LT H C A R E E P I D E M I O L O G Y

INVITED ARTICLE

Robert A. Weinstein, Section Editor

Laboratory-Acquired Infections
Kamaljit Singh
Department of Pathology and Infectious Diseases, Rush University Medical Center, Chicago, Illinois

An estimated 500,000 workers are employed in laboratories in

the United States [1]. These workers are exposed to a variety
of pathogenic microorganisms that may put them at risk of
infection. However, the precise risk posed to individual laboratory workers after an exposure is difficult to determine, in
part because of a lack of systematic reporting. Current available
data are limited to retrospective and voluntary postal surveys,
anecdotal case reports, and reports about selected outbreaks
with specific microorganisms.
Laboratory workers frequently become unwittingly infected
through hitherto unexpected modes of transmission. This was
illustrated by the first laboratory-acquired case of severe acute
respiratory syndrome (SARS) coronavirus, which occurred 4
months after the end of the SARS epidemic [2]. A 27-year-old
microbiology graduate student in Singapore, who was working
with a nonattenuated strain of West Nile virus, was evaluated
for flulike symptoms. The patient denied any exposure to SARS
and had no travel history. He was discharged from the emergency department but returned 5 days later because of persistent fever. Because Singapore remained in a heightened state
of alert for SARS, a polymerase chain reaction assay was perReceived 26 September 2008; accepted 16 February 2009; electronically published 29 May
2009.
Reprints or correspondence: Dr. Kamaljit Singh, Rush University Medical Center, 1653 W.
Congress Pkwy., Chicago, IL 60612 (Kamaljit_Singh@rush.edu).
Clinical Infectious Diseases 2009; 49:1427
 2009 by the Infectious Diseases Society of America. All rights reserved.
1058-4838/2009/4901-0016$15.00
DOI: 10.1086/599104

142 CID 2009:49 (1 July) HEALTHCARE EPIDEMIOLOGY

formed with a sputum specimen and returned a positive result

for SARS coronavirus. Additional epidemiologic investigation
revealed that the laboratory where he worked was also involved
in research on SARS coronavirus and that one of the cell cultures of West Nile virus was contaminated with the same infecting strain of SARS coronavirus. Although this case represents an exceptional event, it serves to highlight the inherent
risk posed to laboratory workers by virtue of their occupation.
Infectious diseases specialists may be asked to evaluate an ill
laboratory worker. This article provides a framework for assessment of such patients by reviewing the published literature
on infections acquired in the clinical diagnostic laboratory.
SURVEYS OF LABORATORY-ACQUIRED
INFECTIONS
Laboratory infections due to a wide variety of bacteria, viruses,
rickettsiae, fungi, and parasites have been described in the literature. The largest survey of infections was reported in 1976
by Pike [3], who found that 4079 laboratory-acquired infections
were due to 159 agents, although 10 agents accounted for 150%
of the cases (table 1) [3, 4]. At least 173 deaths have resulted
from laboratory-acquired infection [5, 6]. However, care should
be taken in the interpretation of historical surveys, because
some infections (e.g., Q fever, Venezuelan equine encephalitis,
and dermatomycoses) occurred predominantly in research and
animal laboratories, and many of these infections (e.g., psittacosis and typhoid) were reported before 1955 [1, 3].

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Laboratory-acquired infections due to a wide variety of bacteria, viruses, fungi, and parasites have been described. Although
the precise risk of infection after an exposure remains poorly defined, surveys of laboratory-acquired infections suggest that
Brucella species, Shigella species, Salmonella species, Mycobacterium tuberculosis, and Neisseria meningitidis are the most
common causes. Infections due to the bloodborne pathogens (hepatitis B virus, hepatitis C virus, and human immunodeficiency
virus) remain the most common reported viral infections, whereas the dimorphic fungi are responsible for the greatest
number of fungal infections. Because of the increasing attention on the role of the laboratory in bioterrorism preparation,
I discuss the risk of laboratory-acquired infection with uncommon agents, such as Francisella tularensis and Bacillus anthracis.
Physicians who care for a sick laboratory worker need to consider the likelihood of an occupationally acquired infection
while advising exposed laboratory workers about postexposure prophylaxis. In addition, physicians should be aware of the
importance of alerting the laboratory if infection with a high-risk agent is suspected.

Table 1. Ten most frequently reported laboratory-associated infections worldwide.

No. of
cases

No. of
deaths

Brucellosis
Q fever
Hepatitis
Typhoid fever

426
280
268
258

5
1
3
20

Tularemia
Tuberculosis

225
194

2
4

Dermatomycoses
Venezuelan equine
encephalitis

162

146

Psittacosis
Coccidioidomycosis

116
93

10
2

Disease

NOTE. Data are for the years 1976 [3] and 1978 [4].

SPECIFIC LABORATORY-ACQUIRED
INFECTIONS
Bacterial Infections

Bacteria account for the largest proportion of infections (43%)

in diagnostic laboratories, with over 37 different species reported [3]. Below, I highlight common causes of infection that
are currently of most concern.
Brucella species. Brucellosis continues to be the most frequently reported laboratory-associated bacterial infection [13
19]. In the United States, Brucella infection is one of the most
common laboratory-acquired infections, accounting for 24%
of laboratory-acquired bacterial infections and 11% of deaths
due to laboratory infection [20]. Aerosolization is the major
source of transmission, but the bacterium can also be transmitted via direct contact. However, in many reported cases, it
has not been possible to accurately determine the mechanism
for transmission. The disease has also affected janitors and
persons who have made brief visits to the laboratory [21].
Person-to-person transmission is rare, although a case of Brucella infection transmitted from a laboratory worker to a spouse
has been documented, presumably through sexual intercourse
[22].
Although no controlled studies have been performed to assess the benefit of postexposure prophylaxis (PEP), it should
be considered for laboratory workers who have high-risk exposure to Brucella species (e.g., because of direct manipulation

Table 2. Laboratory-associated infection and relative risk

of infection, compared with the risk among the general
population.

Organism
Shigella species
Brucella species

No. of
cases of infection

Relative risk
of infection

15
7

1
8012.5

Salmonella species

Staphylococcus aureus
All
MRSA

0.08

6
5

NA
NA

Neisseria meningitidis
Escherichia coli O157:H7
Coccidioides species

4
2
2

40.8
8.6
1.1

Clostridium difficile

0.03

NOTE. Data are for the years 20022004 [11]. MRSA, methicillinresistant S. aureus.

HEALTHCARE EPIDEMIOLOGY CID 2009:49 (1 July) 143

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Surveys of diagnostic laboratory workers in the United Kingdom conducted since 1971 have reported that tuberculosis and
enteric infections (especially shigellosis) were the most common
laboratory-acquired infections [7, 8]. A follow-up survey of UK
laboratories from 19941995 reported that gastrointestinal infections predominated, particularly shigellosis [9]. Similar results were obtained from a survey of clinical microbiology laboratories in Utah from the period 19781992, with shigellosis
reported to be the most common laboratory-acquired infection
[10]. These results suggest a shift in the pattern of laboratoryacquired infections, with enteric infections predominating.
However, no denominator data have been provided that would
help determine the actual risk or incidence of infection for
laboratory workers.
In a 20022004 survey of clinical laboratory directors who
participate in ClinMicroNet, an online forum sponsored by the
American Society of Microbiology, 33% of laboratories reported
the occurrence of at least 1 laboratory-associated infection (table 2) [11]. The 3 most common laboratory-acquired infections
were shigellosis, brucellosis, and salmonellosis. In contrast, the
highest incidences of infection were associated with Brucella
species (641 cases per 100,000 laboratory technologists, compared with 0.08 cases per 100,000 persons in the general population) and Neisseria meningitidis (25.3 cases per 100,000 laboratory technologists, compared with 0.62 cases per 100,000
persons in the general population).
Of note, the annual number of laboratory-acquired infections has steadily decreased since 1965 [3, 5]. For example,
survey results from the United Kingdom from the period 1988
1989 found an infection incidence of 82.7 cases per 100,000
person-years, compared with an incidence of 16.2 cases per
100,000 person-years during the period 19941995 [8, 9]. This
finding undoubtedly reflects an improved awareness of the hazards of working with infectious agents and placement of a

greater emphasis on laboratory safety, such as through the use

of personal protective equipment. In addition, there have been
improvements in laboratory design, such as the use of laminarflow biological safety cabinets (BSCs), which provide unidirectional airflow that entraps any aerosolized particles in the
airstream and subsequently into air filters [12].

144 CID 2009:49 (1 July) HEALTHCARE EPIDEMIOLOGY

imens, and manipulation of specimens or cultures that generate

aerosols is the most important risk factor for acquiring tuberculosis in the laboratory. The high infectivity of M. tuberculosis
is related to the low infective dose for humans (50% infective
dose, !10 bacilli) [28]. The use of laminar-flow BSCs for aerosol-generating manipulations with biosafety level 2 practices
and fit-tested respirators with N-95 rating should be routinely
used [12, 29]. Laboratory personnel should undergo an annual
Mantoux purified protein derivative skin test or an interferong release assay to demonstrate conversion. Persons with positive
test results should be evaluated for active tuberculosis by chest
radiography. In the event of accidental exposure, laboratory
workers should be tested 3 and 6 months after the accident,
and persons with new conversion should be offered prophylaxis
[29].
Francisella tularensis. F. tularensis is a fastidious, gramnegative coccobacillus that is infrequently encountered in the
clinical microbiology laboratory, but it has gained increased
importance because of its possible use as a bioterrorism agent
[30]. The greatest hazard to laboratory workers is from exposure to infectious aerosols from manipulation of cultures.
Clinicians should be aware that, although patients with tularemia, brucellosis, or endemic mycoses do not pose a communicable disease risk to health care workers, specimens obtained from these patients pose a significant threat to laboratory
workers.
Shapiro et al. [31] described 12 laboratory workers who were
exposed to F. tularensis after clinicians failed to notify the laboratory about a suspected case of pneumonic tularemia in a
43-year-old man who eventually died. Blood cultures, sputum
cultures, and autopsy pleural fluid were all positive for gramnegative coccobacilli, which failed to grow on sheep blood agar
and MacConkey agar and were initially misidentified as Haemophilus species. Eleven laboratory workers and 2 autopsy personnel with high-risk exposure to F. tularensis received PEP
with doxycycline (100 mg twice daily for 14 days), with no
resulting infections. To minimize the risk of exposure of laboratory workers, any suspicion about infection with a high-risk
pathogen should be immediately communicated to the laboratory. This practice not only protects the staff but also benefits
the patient, because a faster and more directed laboratory evaluation can be initiated.
Bacillus anthracis. Before the 2001 outbreak of bioterrorism-related anthrax in the United States, anthrax was an uncommon illness in the United States [32]. In March 2002, the
Centers for Disease Control and Prevention were alerted about
a laboratory worker who had received a diagnosis of cutaneous
anthrax [33]. One day after he had cut himself over the right
jaw while shaving, the patient assisted a coworker in moving
vials of B. anthracis from the laminar-flow BSC in the main
laboratory to a freezer. The patient had handled the vials with-

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of Brucella cultures outside of laminar-flow BSCs). Doxycycline

(or trimethoprim-sulfamethoxazole for pregnant women) and
rifampin have been frequently used for PEP [13, 23]. In a report
from Canada, 26 laboratory workers were exposed to Brucella
melitensis, which had been isolated from a patient from India
with a draining chest sinus. Six laboratory workers were offered
PEP with doxycycline (100 mg twice daily) and rifampin (600
mg daily) for 3 weeks. Only 1 person declined PEP; 10 weeks
after exposure, the technologist developed fever (temperature,
40C), and 2 sets of blood cultures confirmed brucellosis.
None of the other laboratory workers developed infection or
evidence of seroconversion. Follow-up serologic tests should
be performed for all exposed individuals, probably every fortnight for the first 3 months, then every month for an additional
69 months [13, 18].
N. meningitidis. Sejvar et al. [24] examined the risk of
laboratory-acquired N. meningitidis infection using postings on
listservs, to obtain reports of laboratory-acquired meningococcal disease occurring worldwide during the period 1985
2001. Sixteen cases of probable laboratory-acquired meningococcal disease were identified, including 6 cases in the United
States. Nine cases (56%) were due to serogroup B, and 7 (44%)
were due to serogroup C. Overall, 8 cases (50%) were fatal. All
cases occurred among clinical microbiologists and were likely
due to exposure to aerosols containing N. meningitidis. The
calculated attack rate was 13 cases per 100,000 microbiologists,
compared with an attack rate of 0.3 cases per 100,000 persons
among the general population. The results of this analysis suggest that laboratory-acquired meningococcal disease represents
a significant occupational hazard to clinical microbiologists.
Although primary prevention of laboratory-acquired meningococcal disease should focus on appropriate handling and manipulation of cultures in a laminar-flow BSC, all laboratory
microbiologists should be offered the tetravalent vaccine [25].
It will decreasebut not eliminatethe risk of infection, because it is less than 100% effective and does not provide protection against serogroup B [26]. Microbiologists who inadvertently manipulate invasive N. meningitidis isolates on an
open bench-top in a manner that could result in aerosolization
should consider PEP with either a single 500-mg dose of ciprofloxacin or 600 mg of rifampin given twice daily for 2 days
[24].
Mycobacterium tuberculosis. Early surveys of laboratoryacquired tuberculosis found an incidence of tuberculosis among
laboratory personnel 39 times greater than that in the general
population [7, 27]. However, unless there is some accident to
which the infection can be traced, it is difficult to state with
certainty that tuberculosis was laboratory acquired, because of
the potential for exposure outside of the workplace and the
long incubation period before symptomatic disease develops.
M. tuberculosis can be isolated from a variety of clinical spec-

Table 3. Laboratory-acquired parasitic infections.

Parasite

No. of cases
(n p 313)

Blood and tissue protozoa

Trypanasoma cruzi

65

Toxoplasma gondii
Plasmodium species
Leishmania species
Trypanosoma brucei

75
52
16
6

Trypanosoma species
Leukocytozoon species

17
1

Intestinal protozoa
Cryptosporidium parvum

16

Isospora belli
Giardia lamblia

8
4
23

Ancyclostoma species
Ascaris lumbricoides

1
8

Enterobius vermicularis
Fasciola hepatica
Sarcocystis species
Hookworm

1
2
1
2

9
6

NOTE. Data are for the years 1976 [3] and 2001 [45].

out gloves but washed his hands with soap and water. Over
the next 3 days, the cut over the laboratory workers jaw increased in size, and he developed low-grade fever, cervical
lymphadenopathy, and cellulitis around the scab. Cultures of
specimens from beneath the scab were positive for B. anthracis,
and the patient was treated with intravenous ciprofloxacin and
doxycycline and discharged while receiving ciprofloxacin.
Epidemiologic investigation of this case revealed that the tops
of the vials tested positive for B. anthracis. Although all specimen processing surfaces were decontaminated with 10% bleach
solution, storage vials were sprayed with 70% isopropyl, because
bleach caused labels to become dislodged. This case brings the
number of cases of bioterrorism-related anthrax identified since
3 October 2001 to 23 and is the first laboratory-acquired case
of bioterrorism-related anthrax.
Enteric pathogens. Salmonellosis is one of the most common reported infections in published surveys [3, 5, 6, 8, 11].
Blaser et al. [34] reported 32 cases of laboratory-acquired typhoid fever in the United States over a 42-month period from
1977 to 1980, representing 11.2% of the sporadic cases of typhoid fever reported in the United States. Of particular concern
was that a number of cases occurred in individuals who had
not directly worked in the microbiology laboratory, including
cases in 2 family members of a microbiologist who worked with
Salmonella culture, 1 of which proved to be fatal. In fact, ty-

Viral Infections

Viral agents transmitted through blood and bodily fluids cause

most of the laboratory-acquired infections in diagnostic laboratories and among health care workers [1]. Although the
viral hemorrhagic fevers incite the most fear and dominate the
imagination of the media and public, the viruses responsible
are rare causes of laboratory infection [3, 4]. However, there
is always the possibility that an agent not previously seen may
be encountered. This occurred in 1967, when 31 workers were
infected while handling tissue specimens from African green
monkeys, with 7 deaths resulting [38]. The causative agent was
named Marburg virus, after the town in Germany where most
cases occurred.
Of the common blood-associated viruses, hepatitis B virus
(HBV) is the most common cause of laboratory-acquired infection [1]. The incidence of HBV infection among all health
care workers in the United States is estimated to be 3.54.6
infections per 1000 workers, which is 24 times than the level
for the general population [39]. It is encouraging that, in the
2 most recent surveys of laboratory-acquired infections in the
United Kingdom, there were no reported cases of HBV infection among laboratory workers [8, 9]. This finding is probably
related to the use of universal precautions when handling blood
specimens, improvements in needleless devices, and the availability of immunization.
Because hepatitis B is a vaccine-preventable disease, all
laboratory workers should be offered the hepatitis B vaccine
without charge. Nonimmunized laboratory workers who have
percutaneous, ocular, or mucous membrane exposure to contaminated blood should receive PEP with hepatitis B immunoglobulin and vaccine [39].
During 20052006, there were 802 confirmed cases of acute
hepatitis C reported to the Centers for Disease Control and
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Entamoeba histolytica
Helminths
Schistosoma species
Strongyloides species

phoid fever has accounted for more reported fatalities than any
other laboratory-acquired infection [5]. Of note, many earlier
reported cases of typhoid fever were associated with mouth
pipetting and handling of proficiency test strainspractices
which are now avoided [1, 35, 36].
In recent surveys, Shigella species was the most frequently
identified agent of laboratory-acquired infection [911]. One
explanation for the large number of reported cases of laboratory-acquired shigellosis is that Shigella species are more virulent and require a much lower inoculum to cause illness.
However, it is also probably true that microbiology laboratory
staff who develop diarrhea are more likely to attempt to establish a cause for their illness, compared with the general
population. A number of other enteric pathogens have also
been identified as less common causes of laboratory-acquired
infection, including Clostridium difficile and Escherichia coli
O157:H7 [11, 37].

Fungi

The dimorphic fungi Blastomyces dermatitidis, Coccidioides immitis, and Histoplasma caspsulatum are responsible for the majority of laboratory-acquired fungal infections in the United
States (table 1) [1, 3, 4]. Although cutaneous infections due to
accidental inoculation are documented, most laboratory-acquired infections are caused by inhalation of infectious conidia
from the mold form, resulting in pulmonary infection. The
mere lifting of a culture plate lid often suffices to cause the
release of large numbers of conidia, and should a sporulating
culture be dropped, millions of conidia would be dispersed.
The risk of infection in the mycology laboratory probably is
low, because handling of specimens is done in laminar-flow
BSCs, and culture plates are secured with shrink seal to prevent
accidental opening. However, a greater risk of infection is likely
on the aerobic culture bench, because colonies of B. dermatitidis
and C. immitis can grow on routine media and may be visible
within 23 days. It cannot be overemphasized that clinicians
who suspect a dimorphic fungal infection should immediately
alert the microbiology laboratory.
Parasites

Laboratory-acquired parasitic infections are uncommon in the

diagnostic microbiology laboratory [1, 3, 6]. Approximately 313
cases of laboratory-acquired infection, with a variety of blood
and intestinal protozoa, have been reported (table 3) [3, 45].
Most of these cases occurred in research and reference laboratories. Readers are referred to the review by Herwaldt [45].
Fifty-two cases of malaria among laboratory workers and
health care workers have been reported, with 34 cases reviewed
by Herwaldt [45]; 10 cases were due to Plasmodium cynomolgi,
146 CID 2009:49 (1 July) HEALTHCARE EPIDEMIOLOGY

9 cases were due to Plasmodium vivax, and 15 cases were due

to Plasmodium falciparum [3, 45]. Most of the cases of P. vivax
and P. falciparum infection occurred among health care workers
and laboratory workers rather than among researchers and resulted from needlestick injuries that occurred while obtaining
blood or preparing blood smears from patients [45]. Infection
due to intestinal protozoa are uncommon in clinical diagnostic
laboratories [45]. One case of giardiasis was reported in a clinical laboratory technologist who processed specimens, many of
which were in leaky containers. One case of Isospora belli infection occurred in a technologist who examined numerous
stool specimens from a patient infected with I. belli.
CONCLUSIONS
Laboratory-acquired infection represents an occupational hazard unique to laboratory workers, especially those in the microbiology laboratory. Exposures may occur inadvertently, may
not even be recalled, or may result from lapses in technique
leading to accidental inoculation. However, not every exposure
results in infection. A risk assessment for infection based on
the hosts immune system, mechanism of the exposure, infectious dose of the exposure, virulence of the agent, use of personal protective equipment, and immunization status needs to
be performed. The accurate quantification of such risk is unfortunately difficult, because there is no systematic reporting
system that monitors the number of laboratory-related exposures and infections. The Centers for Disease Control and Prevention has recently convened a committee to address these
issues that will, I hope, provide evidence-based guidelines on
exposure risk and use of PEP.
Acknowledgments
Potential conflicts of interest. K.S. has served on the speakers bureau
for Wyeth.

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